rs2165427

Positions:

• chr2-101114673-G-A
• chr2-101114673-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330348.2(TBC1D8):​c.128-24309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,176 control chromosomes in the GnomAD database, including 1,669 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1669 hom., cov: 33)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

Genes affected

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D8	NM_001330348.2	c.128-24309C>T		intron_variant		ENST00000409318.2	NP_001317277.1
TBC1D8	NM_001102426.3	c.128-24309C>T		intron_variant			NP_001095896.1
TBC1D8	NR_138475.2	n.257-24309C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D8	ENST00000409318.2	c.128-24309C>T		intron_variant		5	NM_001330348.2	ENSP00000386856	A1
TBC1D8	ENST00000376840.8	c.128-24309C>T		intron_variant		1		ENSP00000366036	P4
TBC1D8	ENST00000463469.5	n.450-24309C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20813 AN: 152058 Hom.: 1666 Cov.: 33

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20826 AN: 152176 Hom.: 1669 Cov.: 33 AF XY: 0.138 AC XY: 10274 AN XY: 74400

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.121

Alfa AF: 0.144 Hom.: 2254

Bravo AF: 0.138

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2165427; hg19: chr2-101731135; COSMIC: COSV65211047; COSMIC: COSV65211047;